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Cancer immunotherapy has emerged as a transformative approach in oncology, utilizing the body's immune system to specifically target and destroy malignant cells. This review explores the scope and impact of various immunotherapeutic strategies, including monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy, checkpoint inhibitors, cytokine therapy, and therapeutic vaccines. Monoclonal antibodies, such as Rituximab and Trastuzumab, have revolutionized treatment paradigms for lymphoma and breast cancer by offering targeted interventions that reduce off-target effects. CAR-T cell therapy presents a potentially curative option for refractory hematologic malignancies, although challenges remain in effectively treating solid tumors. Checkpoint inhibitors have redefined the management of cancers like melanoma and lung cancer; however, managing immune-related adverse events and ensuring durable responses are critical areas of focus. Cytokine therapy continues to play a vital role in modulating the immune response, with advancements in cytokine engineering improving specificity and reducing systemic toxicity. Therapeutic vaccines, particularly mRNA-based vaccines, represent a frontier in personalized cancer treatment, aiming to generate robust, long-lasting immune responses against tumor-specific antigens. Despite these advancements, the field faces significant challenges, including immune resistance, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Future research should address these obstacles through emerging technologies, such as next-generation antibodies, Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based gene editing, and AI-driven drug discovery. By integrating these novel approaches, cancer immunotherapy holds the promise of offering more durable, less toxic, and highly personalized treatment options, ultimately improving patient outcomes and survival rates. [ABSTRACT FROM AUTHOR]

Urease enzyme is a known therapeutic drug target for treatment of Helicobacter pylori infection due to its role in settlement and growth in gastric mucosa. In this study, we designed a new series of sulfonates and sulfamates bearing imidazo[2,1-b]thiazole scaffold that exhibit a potent inhibitory activity of urease enzyme. The most potent compound 2c inhibited urease with an IC50 value of 2.94 ± 0.05 μM, which is 8-fold more potent than the thiourea positive control (IC50 = 22.3 ± 0.031 μM). Enzyme kinetics study showed that compound 2c is a competitive inhibitor of urease. Molecular modeling studies of the most potent inhibitors in the urease active site suggested multiple binding interactions with different amino acid residues. Phenotypic screening of the developed compounds against H. pylori delivered molecules of that possess high potency (1a, 1d, 1h, 2d, and 2f) in comparison to the positive control, acetohydroxamic acid. Additional studies to investigate the selectivity of these compounds against AGS gastric cell line and E. coli were performed. Permeability of the most promising derivatives (1a, 1d, 1h, 2d, and 2f) in Caco-2 cell line, was investigated. As a result, compound 1d presented itself as a lead drug candidate since it exhibited a promising inhibition against urease with an IC50 of 3.09 ± 0.07 μM, MIC value against H. pylori of 0.031 ± 0.011 mM, and SI against AGS of 6.05. Interestingly, compound 1d did not show activity against urease-negative E. coli and exhibited a low permeability in Caco-2 cells which supports the potential use of this compound for GIT infection without systemic effect. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the adhesion and biofilm formation of Candida albicans (C. albicans) on conventionally fabricated, milled, and 3D-printed denture base resin materials in order to determine the susceptibility of denture contamination during clinical use. Specimens were incubated with C. albicans (ATCC 10231) for 1 and 24 h. Adhesion and biofilm formation of C. albicans were assessed using the field emission scanning electron microscopy (FESEM). The XTT (2,3-(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) assay was used for the quantification of fungal adhesion and biofilm formation. The data were analyzed using GraphPad Prism 8.02 for windows. One-way ANOVA with Tukey's post hoc testing were performed with a statistical significance level set at α = 0.05. The quantitative XTT biofilm assay revealed significant differences in the biofilm formation of C. albicans between the three groups in the 24 h incubation period. The highest proportion of biofilm formation was observed in the 3D-printed group, followed by the conventional group, while the lowest candida biofilm formation was observed in the milled group. The difference in biofilm formation among the three tested dentures was statistically significant (p < 0.001). The manufacturing technique has an influence on the surface topography and microbiological properties of the fabricated denture base resin material. Additive 3D-printing technology results in increased candida adhesion and the roughest surface topography of maxillary resin denture base as compared to conventional flask compression and CAD/CAM milling techniques. In a clinical setting, patients wearing additively manufactured maxillary complete dentures are thus more susceptible to the development of candida-associated denture stomatitis and accordingly, strict oral hygiene measures and maintenance programs should be emphasized to patients. [ABSTRACT FROM AUTHOR]

Background: Mobile phones are excessively used even though microbes' ability to survive on phone surfaces was confirmed. During the COVID-19 pandemic, heavy hygiene practices have been applied to mobile surfaces. Therefore, it is interesting to evaluate the emergence of antimicrobial-resistant bacteria on mobile phone surfaces. Methods: A random sampling technique was utilized on residents in Abu Dhabi, UAE between May and June 2021. A swab sample from each participant's mobile phone was collected and transported to the microbiology laboratory for bacterial culture and antimicrobial susceptibility tests. Furthermore, a cross-sectional study was conducted via a self-administered questionnaire filled by participants. The questionnaire was used to collect sociodemographic data, phone frequency usage and cleaning methods. Results: One hundred two-sample swabs and data have been included in the study. The majority of participants (91.1%) reported cleaning their mobile phones with wipes and alcohol. However, 100% of participants had a mobile phone contaminated by bacteria such as S. aureus, E. coli, Coagulase-negative staphylococci, Micrococcus, Bacillus, Streptococcus, Citrobacter, Proteus, Enterococcus, klebsiella, Pseudomonas and Actinobacteria. Interestingly, most of these potentially pathogenic bacteria were found to be resistant to ampicillin, ceftazidime and cefotaxime. Conclusion: The continuous hand and mobile disinfectant have contributed to the emergence of resistant bacteria. [ABSTRACT FROM AUTHOR]

Given the high global prevalence and mortality associated with gastric cancer, and its known causal link with Helicobacter pylori infection, it is important to have a biomarker to identify malignant transformation at early stages. Previously, we, and others, have reported that H. pylori-induced epigenetic changes could mediate carcinogenic transformation of the gastric cells. Also, CXCL1 secreted by gastric cancer cells was reported as a key diagnostic and prognostic biomarker for the pathogenic progression of gastric cancer. In this study, for the first time, we aimed to investigate the role of H. pylori-induced DNA methylation-based epigenetic regulation of CXCL1. In silico analysis of publicly available datasets and in vitro experiments were performed. Our results showed that CXCL1 is highly expressed in both gastric cancer tissues and gastric cancer cells infected with H. pylori. Further, we showed and confirmed that H. pylori-mediated overexpression of CXCL1 is due to hypomethylation of its promoter region. Since epigenetic events such as DNA methylation happen early in the sequence; H. pylori-induced CXCL1 hypomethylation could likely be detected at an early stage of gastric cancer development. Epigenetic modifications, such as CXCL1 hypomethylation, are reversible and could potentially be a therapeutic target using demethylation drugs. [ABSTRACT FROM AUTHOR]

Background: Most breast cancer-related deaths result from metastasis. Understanding the molecular basis of metastasis is needed for the development of effective targeted and preventive strategies. Matrix metalloproteinase-1 (MMP1) plays an important role in brain metastasis (BM) of triple-negative breast cancer (TNBC) by promoting extravasation of cancer cells across the brain endothelium (BE). MMP1 expression is controlled by endogenous microRNAs. Preliminary bioinformatics analysis has revealed that miR-623, known to target the 3ʹUTR of MMP1, is significantly downregulated in brain metastatic tumors compared to primary BC tumors. However, the involvement of miR-623 in MMP1 upregulation in breast cancer brain metastatic cells (BCBMC) remains unexplored. Here, we investigated the role of miR-623 in MMP1 regulation and its impact on the extravasation of TNBC cells through the BE in vitro. Materials and Methods: A loss-and-gain of function method was employed to address the effect of miR-623 modulation on MMP1 expression. MMP1 regulation by miR-623 was investigated by real-time PCR, western blot, luciferase and transwell migration assays using an in vitro human BE model. Results: Our results confirmed that brain metastatic TNBC cells express lower levels of miR-623 compared with cells having low propensity to spread toward the brain. miR-623 binds to the 3′-untranslated region of MMP1 transcript and downregulates its expression. Restoring miR-623 expression significantly decreased MMP1 expression, preserved the endothelial barrier integrity, and attenuated transmigration of BCBMC through the BE. Conclusion: Our study elucidates, for the first time, the crucial role of miR-623 as MMP1 direct regulator in BCBMC and sheds light on miR-623 as a novel therapeutic target that can be exploited to predict and prevent brain metastasis in TNBC. Importantly, the presents study helps in unraveling a brain metastasis-specific microRNA signature in TNBC that can be used as a guide to personalized metastasis prediction and preventive approach with better therapeutic outcome. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is known to colonize gastric mucosa, induce inflammation, and alter gastric microbiota resulting in a spectrum of gastric diseases. Likewise, changes in gut microbiota have recently been linked with various metabolic and inflammatory diseases. While extensive number of studies were published examining the relationship between H. pylori and gastric microbiota, little is known about the impact of H. pylori on downstream gut microbiota. In this study, we performed 16 S rRNA and ITS2-based microbial profiling analysis of 60 stool samples from adult individuals. Remarkably, the gut microbiota of H. pylori infected individuals was shown to be increased of members belonging to Succinivibrio, Coriobacteriaceae, Enterococcaceae, and Rikenellaceae. Moreover, gut microbiota of H. pylori infected individuals was shown to have increased abundance of Candida glabrata and other unclassified Fungi. These results links possible role for H. pylori-associated changes in the gut microbiota in intestinal mucosal barrier disruption and early stage colorectal carcinoma deployment. Altogether, the identified differences in bacterial and fungal composition provides important information that may eventually lead to the development of novel biomarkers and more effective management strategies. [ABSTRACT FROM AUTHOR]

Candida is a serious life.threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. [ABSTRACT FROM AUTHOR]

Gastric ulcer is one of the most common chronic gastrointestinal diseases characterized by a significant defect in the mucosal barrier. Helicobacter pylori (H. pylori) infection and the frequent long-term use of non-steroidal anti-inflammatory drugs are major factors involved in gastric ulcer development. Acid inhibitors and antibiotics are commonly used to treat gastric ulcer. However, in the last few decades, the accumulating evidence for resistance to antibiotics and the side effects of antibiotics and acid inhibitors have drawn attention to the possible use of probiotics in the prevention and treatment of gastric ulcer. Probiotics are live microorganisms that when administered in adequate amounts confer health benefits on the host. Currently, the available experimental and clinical studies indicate that probiotics are promising for future applications in the management of gastric ulcers. This review aims to provide an overview of the general health benefits of probiotics on various systemic and gastrointestinal disorders with a special focus on gastric ulcer and the involved cellular and molecular mechanisms: i) Protection of gastric mucosal barrier; ii) upregulation of prostaglandins, mucus, growth factors and anti-inflammatory cytokines; iii) increased cell proliferation to apoptosis ratio; and iv) induction of angiogenesis. Finally, some of the available data on the possible use of probiotics in H. pylori eradication are discussed. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge, as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and the encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer, presents novel nanomedicine therapeutics aimed at improving the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for the clinical application of nanomedicine in the management of LC resistance. [ABSTRACT FROM AUTHOR]

Aml Mohamed Nada is also affiliated with Internal Medicine, Mansoura University, Mansoura, Egypt. Reference 1 Dash NR, Khoder G, Nada AM, Al Bataineh MT (2019) Exploring the impact of I Helicobacter pylori i on gut microbiome composition. [Extracted from the article]

Simple Summary: The wall of the stomach is easily damaged by different factors leading to serious diseases such as ulcers and cancer. In this study, the effects of a mixture of different types of beneficial bacteria (De Simone Formulation) were investigated in a mouse model of stomach wall damages induced by single or multiple doses of acetylsalicylic acid. Control mice received water. The stomachs of all mice were processed for microscopic examination and labeling of dividing stem cells and stomach cell lineages secreting mucus, acid, pepsin, and hormones. The results reveal beneficial effects for the multiple bacterial strain of De Simone Formulation given before or after the induction of stomach erosions. The regeneration of the stomach wall was associated with an increase in stem cell proliferation and enhanced production of protective factors such as mucus, and restoration of the aggressive factors produced by acid and pepsin secreting cell lineages. Therefore, the protective and therapeutic effects of the multi-strain healthy bacteria against stomach erosions involve modulation of not only dividing stem cells but also the multiple secretory cell lineages of the stomach. Patients with gastric mucosal erosions are predisposed to chronic gastritis, ulcer or even cancer. The repair of mucosal erosions involves several events including proliferation of gastric epithelial stem cells. The aim of this study was to investigate the effects of the probiotic mixture of De Simone Formulation on gastric epithelial stem cell lineages in mouse models of gastric mucosal erosions. Gastric erosions were induced by a single oral gavage of 80% ethanol containing 15 mg/mL acetylsalicylic acid (5 mL/kg) following a daily dose of probiotic mixture (5 mg/day/mouse) for 10 days. In another protocol, erosions were induced by a daily gavage of acetylsalicylic acid (400 mg/kg/day/mouse) for 5 days before or after daily administration of probiotic mixture for 5 days. Control mice received water gavage for 10 days. All mice were injected with bromodeoxyuridine two hours before sacrifice to label S-phase cells. The stomachs of all mice were processed for histological examination, lectin binding, and immunohistochemical analysis. The results reveal that mice that received probiotics before or after the induction of erosion showed a decrease in erosion index with an increase in gastric epithelial stem/progenitor cell proliferation and enhanced production of mucus, trefoil factors, and ghrelin by mucous and enteroendocrine cell lineages. These mice also showed restoration of the amount of H+,K+-ATPase and pepsinogen involved in the production of the harsh acidic environment by parietal and chief cell lineages. In conclusion, this study demonstrates the beneficial effects of probiotics against gastric mucosal erosion and highlights the involvement and modulation of proliferative stem cells and their multiple glandular epithelial cell lineages. [ABSTRACT FROM AUTHOR]

Simple Summary: Helicobacter pylori (H. pylori) has been classified as a Class I carcinogen by the International Agency of Research on Cancer (IARC) and has been identified as the most common etiologic agent of infection-associated cancers. Early detection and eradication of H. pylori can definitely lead to long-term healing of all H. pylori-related diseases. In Lebanon, the prevalence of H. pylori is not well documented, especially in healthy subjects. A cross-sectional study was conducted on 300 healthy Lebanese volunteers, including both children and adults. Interestingly, a significant correlation was found between H. pylori infection and sheesha smoking. These findings highlight the need for the development of preventive approaches and strategic indications for the appropriate management of H. pylori infections in Tripoli, North Lebanon. Helicobacter pylori (H. pylori) infection occurs among half of the general population worldwide, with high geographic variability. Even though H. pylori is the leading cause of several gastric diseases, ranging from gastritis and peptic ulcers to gastric malignancies, such as gastric cancer and mucosa-associated lymphoid tissue lymphoma, most of the infections remain asymptomatic. Early detection and eradication of H. pylori can definitely prevent severe long-term gastric diseases associated with H. pylori. In Lebanon, the prevalence of H. pylori is not well documented, especially in healthy subjects. The aim of this study is to assess H. pylori infections and the associated risk factors in Tripoli, North Lebanon. A cross-sectional study was conducted on 300 healthy Lebanese volunteers, including both children and adults. The H. pylori stool antigens were detected using the Premier Platinum HpSA test. The socio-demographic data, lifestyle characteristics, and gastrointestinal characteristics of all participants were analyzed. Out of the 300 tested volunteer subjects, 31% were found to be positive for H. pylori. A multivariate binary logistic regression analysis for factors associated with H. pylori infection revealed a significant association between H. pylori infection and gastrointestinal disturbances, the crowding index, and occupation. A significant statistical correlation was found between sheesha smoking (p = 0.001) and H. pylori infection. These findings highlight the need for the development of preventive approaches and strategic indications for the appropriate treatment of H. pylori infections in Tripoli, North Lebanon. [ABSTRACT FROM AUTHOR]

Gastric cancer is among the most common malignancies worldwide. Due to limited availability of therapeutic options, there is a constant need to find new therapies that could target advanced, recurrent, and metastatic gastric cancer. Carnosic acid is a naturally occurring polyphenolic abietane diterpene derived from Rosmarinus officinalis and reported to have numerous pharmacological effects. In this study, the cytotoxicity assay, Annexin V-FITC/PI, caspases 3, 8, and 9, cell cycle analysis, and Western blotting were used to assess the effect of carnosic acid on the growth and survival of human gastric cancer cell lines (AGS and MKN-45). Our findings showed that carnosic acid inhibited human gastric cancer cell proliferation and survival in a dose-dependent manner. Additionally, carnosic acid is found to inhibit the phosphorylation/activation of Akt and mTOR. Moreover, carnosic acid enhanced the cleavage of PARP and downregulated survivin expression, both being known markers of apoptosis. In conclusion, carnosic acid exhibits antitumor activity against human gastric cancer cells via modulating the Akt-mTOR signaling pathway that plays a crucial role in gastric cancer cell proliferation and survival. [ABSTRACT FROM AUTHOR]

Optimum Inhibition of Amphotericin-B-Resistant Candida albicans Strain in Single- and Mixed-Species Biofilms by Candida and Non-Candida Terpenoids. Therefore, this information was changed by the Biomolecules Editorial Office from: B Hidaya F.Z. Touil SP 1 sp , Kebir Boucherit SP 1,2 sp , Zahia Boucherit-Otmani SP 1 sp , Ghalia Kohder SP 3,4 sp , Mohamed Madkour SP 3,5 sp and Sameh S. M. Soliman SP 3,4,6, sp * b To: B Hidaya F.Z. Touil SP 1 sp , Kebir Boucherit SP 1,2 sp , Zahia Boucherit-Otmani SP 1 sp , Ghalia Khoder SP 3,4 sp , Mohamed Madkour SP 3,5 sp and Sameh S. M. Soliman SP 3,4,6, sp * b We apologize for any inconvenience caused to the readers. Reference 1 Touil H.F.Z., Boucherit K., Boucherit-Otmani Z., Kohder G., Madkour M., Soliman S.S.M. Optimum Inhibition of Amphotericin-B-Resistant Candida albicans Strain in Single- and Mixed-Species Biofilms by Candida and Non-Candida Terpenoids. [Extracted from the article]

Probiotics are used in the management of some gastrointestinal diseases. However, little is known about their effects on normal gastric epithelial biology. The aim of this study was to explore how the probiotic mixture VSL#3 affects gastric cell lineages in mice with a special focus on protective and aggressive factors. Weight-matching littermate male mice (n = 14) were divided into treated and control pairs. The treated mice received VSL#3 (5 mg/day/mouse) by gastric gavage for 10 days. Control mice received only the vehicle. Food consumption and bodyweight were monitored. All mice were injected intraperitoneally with bromodeoxyuridine (120 mg/Kg bodyweight) two hours before sacrificed to label S-phase cells. Stomach tissues were processed for lectin- and immunohistochemical examination. ImageJ software was used to quantify immunolabeled gastric epithelial cells. Real-time quantitative polymerase chain reaction was used to provide relative changes in expression of gastric cell lineages specific genes. Results revealed that treated mice acquired (i) increased production of mucus, trefoil factor (TFF) 1 and TFF2, (ii) decreased production of pepsinogen, and (iii) increased ghrelin-secreting cells. No significant changes were observed in bodyweight, food consumption, cell proliferation, or parietal cells. Therefore, VSL#3 administration amplifies specific cell types specialized in the protection of the gastric epithelium. [ABSTRACT FROM AUTHOR]

The United Arab Emirates (UAE) has been under continuous populational influences from Asia, Europe, and Africa, making it an ideal site for epidemiological studies on Helicobacter pylori. However, there has been a paucity of well-designed prevalence studies on H. pylori from UAE. The aim of this study was to determine the prevalence of H. pylori and its associated risk factors in the UAE. A prospective cross-sectional study was conducted on healthy asymptomatic residents of UAE. Socio-demographic, lifestyle, and gastrointestinal characteristics of participants were obtained through a questionnaire in parallel within the stool sample collection. A total of 350 participants were included in this study and were tested for H. pylori using the stool antigen test (Premier Platinum HpSAT). Out of the total tested study participants, 41% were found to be H. pylori-infected. Logistic regression analysis has shown a significant association between H. pylori infection and gender, age, ethnicity, profession, domestic overcrowding, source of drinking water, and gastrointestinal characteristics of participants. Based on the results from this study, we suggest that preventive measures against H. pylori infection should be considered worthy by public health authorities. [ABSTRACT FROM AUTHOR]

Gastric cancer is ranked fifth in cancer list and has the third highest mortality rate. Helicobacter pylori is a class I carcinogen and a predominant etiological factor of gastric cancer. H. pylori infection may induce carcinogenesis via epigenetic alterations in the promoter region of various genes. H. pylori is known to induce hypermethylation-silencing of several tumor suppressor genes in H. pylori-infected cancerous and H. pylori-infected non-cancerous gastric mucosae. This article presents a review of the published literature mainly from the last year 15 years. The topic focuses on H. pylori-induced DNA methylation linked to gastric cancer development. The authors have used MeSH terms "Helicobacter pylori" with "epigenetic," "DNA methylation," in combination with "gastric inflammation", gastritis" and "gastric cancer" to search SCOPUS, PubMed, Ovid, and Web of Science databases. The success of epigenetic drugs such as de-methylating agents in the treatment of certain cancers has led towards new prospects that similar approaches could also be applied against gastric cancer. However, it is very important to understand the role of all the genes that have already been linked to H. pylori-induced DNA methylation in order to in order to evaluate the potential benefits of epigenetic drugs. [ABSTRACT FROM AUTHOR]

Background: Most breast cancer-related deaths result from metastasis. Understanding the molecular basis of metastasis is needed for the development of effective targeted and preventive strategies. Matrix metalloproteinase-1 (MMP1) plays an important role in brain metastasis (BM) of triple-negative breast cancer (TNBC) by promoting extravasation of cancer cells across the brain endothelium (BE). MMP1 expression is controlled by endogenous microRNAs. Preliminary bioinformatics analysis has revealed that miR-623, known to target the 3'UTR of MMP1, is significantly downregulated in brain metastatic tumors compared to primary BC tumors. However, the involvement of miR-623 in MMP1 upregulation in breast cancer brain metastatic cells (BCBMC) remains unexplored. Here, we investigated the role of miR-623 in MMP1 regulation and its impact on the extravasation of TNBC cells through the BE in vitro., Materials and Methods: A loss-and-gain of function method was employed to address the effect of miR-623 modulation on MMP1 expression. MMP1 regulation by miR-623 was investigated by real-time PCR, western blot, luciferase and transwell migration assays using an in vitro human BE model., Results: Our results confirmed that brain metastatic TNBC cells express lower levels of miR-623 compared with cells having low propensity to spread toward the brain. miR-623 binds to the 3'-untranslated region of MMP1 transcript and downregulates its expression. Restoring miR-623 expression significantly decreased MMP1 expression, preserved the endothelial barrier integrity, and attenuated transmigration of BCBMC through the BE., Conclusion: Our study elucidates, for the first time, the crucial role of miR-623 as MMP1 direct regulator in BCBMC and sheds light on miR-623 as a novel therapeutic target that can be exploited to predict and prevent brain metastasis in TNBC. Importantly, the presents study helps in unraveling a brain metastasis-specific microRNA signature in TNBC that can be used as a guide to personalized metastasis prediction and preventive approach with better therapeutic outcome., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Hammash et al.)

Candida albicans is one of the most common human fungal pathogens and represents the most important cause of opportunistic mycoses worldwide. Surgical devices including catheters are easily contaminated with C. albicans via its formation of drug-resistant biofilms. In this study, amphotericin-B-resistant C. albicans strains were isolated from surgical devices at an intensive care center. The objective of this study was to develop optimized effective inhibitory treatment of resistant C. albicans by terpenoids, known to be produced naturally as protective signals. Endogenously produced farnesol by C. albicans yeast and plant terpenoids, carvacrol, and cuminaldehyde were tested separately or in combination on amphotericin-B-resistant C. albicans in either single- or mixed-infections. The results showed that farnesol did not inhibit hyphae formation when associated with bacteria. Carvacrol and cuminaldehyde showed variable inhibitory effects on C. albicans yeast compared to hyphae formation. A combination of farnesol with carvacrol showed synergistic inhibitory activities not only on C. albicans yeast and hyphae, but also on biofilms formed from single- and mixed-species and at reduced doses. The combined terpenoids also showed biofilm-penetration capability. The aforementioned terpenoid combination will not only be useful in the treatment of different resistant Candida forms, but also in the safe prevention of biofilm formation.

Gastric cancer is the fourth most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Recent research suggests that tissue stem cells and the self renewal transcription factor, octamer-binding transcription factor 4 (Oct4), could be involved in the development of certain tumors. The aim of this study was to investigate the expression pattern of Oct4 in normal human stomach and during multistep gastric carcinogenesis. Pyloric antral mucosal tissues were obtained from consenting individuals undergoing endoscopy (due to upper gastrointestinal symptoms) and gastrectomy (due to pyloric antral adenocarcinoma). Some tissue samples were processed to assemble an array of tissue sections representing multistep carcinogenesis and probed using anti-Oct4 antibodies and lectins specific for α-L-fucose or N-acetyl-D-glucosamine. Some tissue samples were processed for subcellular fractionation and western blot analysis using the same antibodies. The results revealed that Oct4-expressing cells were found in the proliferative cell compartment of the pit-gland units of microscopically normal gastric mucosal biopsies. Mucosal tissues with evidence of severe gastritis, metaplastic/dysplastic transformation and gastric cancer showed a significant increase in the expression of Oct4 (the labeled area increased from 2% in the control to 6 and 16% in the gastritis and cancerous tissues, respectively), suggesting a role for Oct4 in the early stages of cancer development. Furthermore, the data revealed an alteration in the subcellular distribution of Oct4, possibly due to the inhibition of cytoplasm-to-nucleus translocation during carcinogenesis. In conclusion, this study demonstrates an alteration in the expression pattern and nuclear translocation of Oct4 during gastric carcinogenesis and may be helpful in designing new modalities for the early detection and/or therapy of gastric cancer.

Aim: To test whether the expression and activity of H,K-ATPase in parietal cells would be affected by cigarette smoke extract., Methods: Extracts of cigarette smoke were administered into mice by gastric gavage (5 mg/kg body weight/day) for 3 d or in drinking water for 7 or 14 d. For the latter, each day a mouse consumed 5 mL water containing extracts of two cigarettes, on average. Control littermate mice received only vehicle. To compare the amount of H,K-ATPase in control and smoke-treated mice, the stomach was processed for Western blotting and immunohistochemical analysis using monoclonal antibodies specific for alpha- or beta-subunits of H,K-ATPase. The p-nitrophenylphosphatase activity assay was used as a measurement for K-dependent H,K-ATPase activity., Results: Probed transblots showed an increase in the amount of H,K-ATPase in smoke-treated mice which was confirmed by immunohistochemistry and was found to be due to increased amounts of protein per parietal cell rather than an increased parietal cell number. The increase in the amount of H,K-ATPase was associated with an enhancement of its enzymatic activity. K-dependent activity in control and smoke-treated mice was significantly different (respectively, 0.12 micromol/mg vs 0.27 micromol/mg per minute, P < 0.05)., Conclusion: Administration of cigarette smoke extract is associated with an increase in the amount and activity of H,K-ATPase and hence, smokers are susceptible to development of peptic ulcer.

To date no reliable diagnostic method exists to predict, among the very large and clinically heterogeneous group of Helicobacter pylori-infected patients, the extremely small group at risk for developing low-grade gastric MALT lymphoma (LG-MALT). Search of proteomic biomarkers holds promise for the classification of the H. pylori strains with regard to this severe clinical outcome. In the present study 69 H. pylori strains isolated from patients with two different H. pylori-associated diseases, duodenal ulcer (DU, n=29) and LG-MALT (n=40) were used. Protein expression patterns of the strains were analyzed by using the high-throughput methodology SELDI. Selected proteins were purified by means of chromatographic and electrophoretic methods in view of further sequencing by LC-MS/MS. Univariate analysis (Mann-Whitney test) of the protein expression patterns generated nine significant biomarkers that can discriminate between H. pylori strains from patients with DU and LG-MALT. These biomarkers are of low molecular weight, ranging from 6 to 26.6 kDa. Among them, two are overexpressed in LG-MALT strains and seven - in DU strains. Two biomarker proteins, one overexpressed in LG-MALT strains (13.2 kDa) and another one - overexpressed in DU strains (26.6 kDa), were purified to homogeneity and identified by using LC-MS/MS as a 50S ribosomal protein L7/L12 and a urease subunit, respectively. These biomarkers can be included in novel protein arrays for the differential diagnosis of H. pylori-associated clinical outcomes., (Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)